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Joint rule with Justin I (his uncle), 4 April - 1 August 527 A.D.Justinian I served his uncle, Emperor Justin I, throughout his reign formulating most imperial policy. Recognizing his brilliance, he was rapidly promoted and in the final months of Justin's reign, he was made co-emperor. Justinian's sole rule began on 1 August 527 and lasted almost four decades during which he re-conquered much of the empire lost during the preceding century, including North Africa, Italy, and parts of Spain. He is well known for his codification of the legal system. His grand scale building program included St Sophia, which still stands as the centerpiece of modern Istanbul. Unfortunately, his ambitious efforts strained the empire's resources and depleted the treasure built by Anastasius. Most of the territory he gained was lost shortly after his death.

The ruins of Antioch on the Orontes lie near the modern city of Antakya, Turkey. Founded near the end of the 4th century B.C. by Seleucus I Nicator, one of Alexander the Great's generals, Antioch's geographic, military and economic location, particularly the spice trade, the Silk Road, the Persian Royal Road, benefited its occupants, and eventually it rivaled Alexandria as the chief city of the Near East and as the main center of Hellenistic Judaism at the end of the Second Temple period. Antioch is called "the cradle of Christianity,” for the pivotal early role it played in the emergence of the faith. It was one of the four cities of the Syrian tetrapolis. Its residents are known as Antiochenes. Antioch was renamed Theoupolis after it was nearly destroyed by an earthquake on 29 November 528. Once a great metropolis of half a million people, it declined to insignificance during the Middle Ages because of warfare, repeated earthquakes and a change in trade routes following the Mongol conquests, which then no longer passed through Antioch from the far east.